Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk

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Abstract

Background: Alterations of the HER2 (also known as erbB-2 or neu) proto- oncogene have been implicated in the carcinogenesis and prognosis of breast cancer. A polymorphism at codon 655 (GTC/valine to ATC/isoleucine [Val655Ile]) in the transmembrane domain-coding region of this gene has been identified and may be associated with the risk of breast cancer. We evaluated this hypothesis in a subgroup of women who participated in a large- scale, population-based, case-control study of breast cancer in Shanghai, China. Methods: Genomic DNA from 339 patients with breast cancer and 361 healthy control subjects was examined for the Val655Ile polymorphism with a polymerase chain reaction-restriction fragment-length polymorphism-based assay. All study subjects completed a structured questionnaire during an in- person interview. All P values are from two-sided tests. Results: We found that 25.1% of the case patients and 21.7% of the control subjects were heterozygous for the Val allele and 3.2% of the case patients and 0.3% of the control subjects were homozygous for this allele (P = .005). Compared with women with the Ile/Ile genotype, women who had the Ile/Val or Val/Val genotype had an elevated risk of breast cancer (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 1.02.0; P = .05) after adjustment for age, educational level, study period, history of breast fibroadenoma, leisure physical activity, and age at first live birth. The risk was elevated even more among women who were homozygous for the Val allele (OR = 14.1; 95% CI = 1.8-113.4). The association was more pronounced among younger women (≤45 years) than among older women (>45 years). The adjusted OR associated with the Val allele was 1.7 (95% CI = 1.1-2.6) for younger women and 1.0 (95% CI = 0.5-1.9) for older women. Conclusions: Results of this study suggest that polymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women.

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CITATION STYLE

APA

Xie, D., Shu, X. O., Deng, Z., Wen, W. Q., Creek, K. E., Dai, Q., … Zheng, W. (2000). Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. Journal of the National Cancer Institute, 92(5), 412–417. https://doi.org/10.1093/jnci/92.5.412

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